What baseline and follow‑up laboratory tests and monitoring (renal function, electrolytes, thyroid panel, liver panel, and ECG if >55 years or cardiac disease) are recommended for a patient on lithium and bupropion?

Laboratory Monitoring for Patients on Lithium and Bupropion

Baseline Laboratory Testing Before Initiation

Before starting lithium, obtain a comprehensive baseline panel including complete blood count, thyroid function tests (TSH and free T4), urinalysis, blood urea nitrogen, serum creatinine with estimated glomerular filtration rate (eGFR), serum calcium, and pregnancy test in individuals of childbearing potential. 1

Lithium-Specific Baseline Tests

• Complete blood count (CBC) with differential to document pre-existing cytopenias and identify contraindications such as severe baseline neutropenia or thrombocytopenia 1
• Thyroid function tests (TSH, free T4) as lithium-induced hypothyroidism develops in approximately 20-30% of patients on long-term therapy, with women under 60 years at higher risk 1
• Renal function panel (BUN, creatinine, eGFR) and urinalysis to establish baseline kidney function, as lithium causes nephrogenic diabetes insipidus in 20-40% of patients within weeks of initiation 2, 3
• Serum calcium and consider parathyroid hormone (PTH) since hypercalcemia occurs in approximately 25% of long-term lithium patients 1
• Pregnancy test in all females of childbearing potential, as lithium exposure during pregnancy carries teratogenic risk 1

Bupropion-Specific Baseline Tests

• Electrocardiogram (ECG) if patient is >55 years or has cardiac disease, as bupropion can cause QRS widening and QTc prolongation in overdose, though therapeutic doses show minimal cardiac effects 4, 5
• Blood pressure measurement as bupropion can cause supine blood pressure elevation and may exacerbate baseline hypertension 5
• Liver function tests are not routinely required for bupropion alone but should be obtained if concurrent hepatotoxic medications are used 6

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Ongoing Monitoring Schedule During Maintenance Therapy

Lithium Monitoring Every 3 Months

Check serum lithium levels every 3 months during stable maintenance therapy, with target therapeutic range of 0.6-1.0 mEq/L for maintenance (0.8-1.2 mEq/L for acute treatment). 1

• Lithium levels should be drawn 12 hours post-dose (morning sample before taking the dose) to ensure accurate interpretation 7
• Increase monitoring frequency to 1-2 weeks after dose adjustments, addition of interacting medications (NSAIDs, ACE inhibitors, ARBs, thiazide diuretics), changes in renal function, or significant weight changes 1

Renal and Metabolic Monitoring Every 6 Months

Monitor renal function (BUN, creatinine, eGFR), electrolytes, thyroid function (TSH), and serum calcium every 6 months during stable maintenance therapy. 1

• If eGFR <60 mL/min/1.73 m², increase monitoring frequency and consider more frequent lithium level checks 1
• If eGFR <30 mL/min/1.73 m², monitor at least monthly and reassess the risk-benefit of continuing lithium 1
• Creatinine increase >50% from baseline or >266 μmol/L triggers review of other nephrotoxic medications and consideration of dose reduction 1
• Creatinine increase >100% from baseline or >310 μmol/L requires discontinuation of lithium 1
• Potassium >5.5 mmol/L requires review of lithium dose and consideration of temporary discontinuation 1

Additional Monitoring Considerations

• Weight assessment and blood pressure annually to monitor for metabolic changes 1
• Urine osmolality or specific gravity if polyuria or polydipsia develops, as nephrogenic diabetes insipidus is common 8
• Perform comprehensive metabolic panel 2-4 weeks after starting lithium to capture early renal function changes 1

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Special Circumstances Requiring Intensified Monitoring

High-Risk Situations

• Patients taking NSAIDs require increased monitoring frequency and avoidance of concomitant use when possible, as NSAIDs significantly increase lithium toxicity risk 1
• During acute illness (fever, vomiting, diarrhea, dehydration), check lithium levels more frequently and maintain hydration 1
• If serious intercurrent illness develops that increases acute kidney injury risk (especially if eGFR <60 mL/min/1.73 m²), temporarily discontinue lithium 1

Patients with Reduced Renal Function

• Patients with impaired renal function require more frequent monitoring than the standard 3-6 month interval, with monthly monitoring when eGFR <30 mL/min/1.73 m² 1
• Up to 30% increase in creatinine from baseline is within acceptable range and does not require immediate intervention 1

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Critical Safety Monitoring

Signs of Lithium Toxicity to Educate Patients About

Instruct patients to interrupt therapy and contact providers immediately upon onset of unexplained anorexia, nausea, vomiting, dark urine, persistent fatigue, coarse tremor, confusion, or ataxia. 6, 2

• Fine tremor, nausea, and diarrhea are common side effects that typically require only dose adjustment 2
• Coarse tremor, confusion, or ataxia indicate potential toxicity requiring immediate medical attention 1

Bupropion Cardiac Monitoring

• ECG monitoring is not routinely required during therapeutic bupropion use in patients without cardiac disease 5
• In patients >55 years or with cardiac disease, obtain baseline ECG and monitor blood pressure at follow-up visits, as bupropion can cause supine blood pressure elevation 5
• Bupropion does not cause significant conduction complications or exacerbate ventricular arrhythmias at therapeutic doses, though it may exacerbate baseline hypertension in some patients 5

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Common Pitfalls to Avoid

• Never rely solely on serum creatinine alone—always calculate eGFR using prediction equations, as serum creatinine can be influenced by extrarenal factors and is less useful when GFR is only mildly impaired 8
• Do not wait beyond 7-8 days to check lithium levels after initiation or dose change, as steady state is achieved in 7-10 days (approximately 5-7 half-lives) 1
• Avoid checking lithium levels at random times—always draw 12 hours post-dose for accurate interpretation 7
• Do not overlook drug interactions—NSAIDs, ACE inhibitors, ARBs, and thiazide diuretics significantly increase lithium levels and toxicity risk 1
• Baseline testing is no longer routinely indicated solely based on age >35 years, but should be considered on an individual basis, particularly for patients taking other medications for chronic conditions 6